| 1999 |
Fission yeast condensin contains five subunits including Cut3/SMC4 and Cut14/SMC2, and Cdc2 kinase directly phosphorylates Cut3/SMC4 at T19 in vitro and in vivo (maximal at metaphase). Alanine substitution of T19 prevents nuclear accumulation during mitosis and causes condensation defects, demonstrating that Cdc2 phosphorylation of SMC4 is required for its mitosis-specific nuclear localization and chromosome condensation. |
In vitro Cdc2 kinase assay, in vivo phosphorylation analysis, GFP localization, temperature-sensitive mutant rescue, alanine substitution mutagenesis |
Genes & development |
High |
10485849
|
| 2001 |
Drosophila SMC4 (encoded by the gluon locus) is required specifically for sister chromatid resolution during mitosis. Loss-of-function mutations allow normal longitudinal axis shortening but cause striking failure of sister chromatid resolution prior to anaphase, leading to chromosome breakage and apoptosis. DmSMC4 localizes to the axial chromosome core at metaphase/anaphase and dissociates during telophase decondensation. |
Genetic loss-of-function (gluon mutant alleles), immunolocalization, cytological analysis of mitotic chromosome structure |
Current biology : CB |
High |
11267866
|
| 2000 |
Human SMC4 (hCAP-C) forms a heterodimeric complex with hCAP-E/SMC2 in HeLa cells. Co-immunoprecipitation of this complex identified CNAP1 (homolog of Xenopus XCAP-D2) as an interacting partner, establishing the existence of a condensin complex in human cells. Chromosome association of the hCAP-C-hCAP-E complex is mitosis-specific, with the complex sequestered in the cytoplasm during interphase, though a subpopulation remains on chromosomes as foci that colocalize with phospho-H3 clusters at late G2/early prophase. |
Co-immunoprecipitation from HeLa extracts, immunofluorescence localization, cell cycle analysis |
Molecular and cellular biology |
High |
10958694
|
| 2003 |
Vertebrate cells contain two distinct condensin complexes (condensin I and condensin II) that share the same SMC2/SMC4 heterodimeric core but differ in their non-SMC subunits. siRNA depletion of condensin I- or condensin II-specific subunits produces distinct chromosome morphology defects; the two complexes show different distributions along the mitotic chromosome axis in vivo and in Xenopus egg extracts. |
siRNA depletion in HeLa cells, Xenopus egg extract reconstitution, immunofluorescence, biochemical fractionation |
Cell |
High |
14532007
|
| 2015 |
Cross-linking mass spectrometry combined with molecular modelling of the chicken SMC2/SMC4 subcomplex reveals that the coiled-coil segments can be closely apposed along their lengths in isolated condensin complexes and in situ in mitotic chromosomes. Both histone H2A and H4 were identified as potential condensin chromatin-interaction partners via cross-linking data. |
Amino acid-selective cross-linking and mass spectrometry, homology modelling, in situ cross-linking on mitotic chromosomes |
Open biology |
Medium |
25716199
|
| 2016 |
High-speed atomic force microscopy in liquid demonstrates that the Smc2-Smc4 coiled-coil arms of S. cerevisiae condensin are highly flexible polymers (persistence length ~4 nm) that dynamically interconvert between multiple architectures. The SMC head domains engage not only with each other but also with the hinge domain at the other end of the ~45-nm coiled coil. |
High-speed atomic force microscopy (AFM) in liquid, quantitative polymer physics analysis |
Cell reports |
High |
26904946
|
| 2018 |
Macrophage Smc4 promotes inflammatory innate immune responses by epigenetically enhancing NEMO (IKKγ) transcription: Smc4 recruits H4K5 acetyltransferase activity to the nemo promoter, increasing H4K5 acetylation and enabling stronger NF-κB and IRF3 activation upon TLR or viral stimulation. Smc4 knockdown or deficiency reduced IL-6, TNF-α, and IFN-β production and protected mice from sepsis. |
High-throughput epigenetic modifier screen, ChIP for H4K5ac at nemo promoter, Smc4 knockdown in macrophages, in vivo sepsis model |
Journal of autoimmunity |
Medium |
29803706
|
| 2019 |
Budding yeast Smc4 protein abundance is cell cycle regulated: it peaks at mitosis and falls to low levels in interphase. Smc4 degradation at the end of mitosis is dependent on the Anaphase Promoting Complex/Cyclosome (APC/C) and mediated by the proteasome. Unexpectedly, the Mad2 spindle checkpoint protein is required for mitotic Smc4 degradation. Overproduction of Smc4 delays decondensation but cannot promote premature condensation in interphase. |
Cell cycle synchronization, protein stability assays, APC/C and Mad2 genetic/chemical perturbation, proteasome inhibition |
Oncotarget |
Medium |
30719224
|
| 2020 |
In Plasmodium spp., SMC2/SMC4 localize to centromeres (validated by co-localization with NDC80 and ChIP-seq) during early schizogony without forming condensin I or II complexes. In mature schizonts and during male gametogenesis, SMC2/SMC4 distribute diffusely and assemble into both condensin I and II complexes. Knockdown of smc2 and smc4 reveals essential roles in parasite proliferation and transmission. |
ChIP-seq, fluorescence microscopy co-localization with NDC80, conditional knockdown, parasite transmission assays |
Cell reports |
Medium |
32049018
|
| 2023 |
SMC4 attenuation in colorectal cancer cells drives a diapause-like state by: (1) promoting expression of three investment-phase glycolysis enzymes and increasing lactate, which via histone lactylation upregulates ABC transporters causing chemoresistance; and (2) acting as a co-activator of PGAM1 transcription, such that combined SMC4/PGAM1 loss impairs F-actin assembly, causes cytokinesis failure and polyploidy, and inhibits proliferation. |
SMC4 knockdown/attenuation, metabolic assays (lactate, glycolysis), histone lactylation ChIP, transcriptional co-activation assays, F-actin imaging, polyploidy quantification |
Cell metabolism |
Medium |
37543034
|
| 2022 |
TREM-1 interacts directly with SMC4 in cardiomyocytes under septic conditions, and inhibition of either TREM-1 or SMC4 prevents NLRP3 inflammasome activation and reduces Gasdermin-D cleavage, IL-1β, and caspase-1 cleavage, identifying SMC4 as a component of the TREM-1/NLRP3 pyroptosis pathway in cardiomyocytes. |
Co-immunoprecipitation (TREM-1/SMC4 interaction), siRNA knockdown, LPS/nigericin pyroptosis model, in vivo CLP sepsis model |
The FEBS journal |
Medium |
36181338
|
| 2025 |
SMC4 promotes prostate cancer cell proliferation and metastasis through the Rheb/mTOR signaling pathway. IP-MS identifies GLUT1 (SLC2A1) as an SMC4 interactor, confirmed by co-IP, and SMC4 knockdown inhibits glycolysis rate and ATP production, linking SMC4 to metabolic regulation via GLUT1 interaction. |
CRISPR/Cas9 SMC4 knockdown, IP-MS interactome, co-IP validation of SMC4-GLUT1 interaction, glycolytic rate assay, in vivo murine lung metastasis model, mTOR/Rheb pathway western blotting |
Advanced science |
Medium |
40278414
|
| 2025 |
SMC4 in triple-negative breast cancer maintains genomic stability to suppress cGAS-STING-mediated type I interferon production and CD8+ T cell recruitment; it also upregulates PD-L1 in a STING-independent manner. Knockdown of SMC4 restored tumor immunogenicity and potentiated anti-PD-1 therapy in immunocompetent 4T1 murine models. |
SMC4 knockdown/overexpression, cGAS-STING pathway assays, ELISA for cytokines, flow cytometry of CD8+ T cells, molecular docking, immunoprecipitation, in vivo 4T1 tumor model with anti-PD-1 |
International immunopharmacology |
Medium |
40976049
|
| 2024 |
FoxO1 promotes SMC4 transcription by binding to the SMC4 promoter at the -1400/-1390 bp region (validated by ChIP-seq and dual-luciferase assay), and also transcriptionally activates METTL14, which increases SMC4 mRNA m6A methylation on its coding sequence, thereby increasing SMC4 mRNA abundance. |
ChIP-seq, dual-luciferase reporter assay, METTL14 knockdown, m6A methylation mapping, in vitro and in vivo proliferation assays |
Cancer science |
Medium |
38403332
|
| 2025 |
Nuclear factor I A (NFIA) directly binds two motifs in the SMC4 promoter (-1379 bp and -354 bp), driving SMC4 transcription, as validated by dual-luciferase and ChIP assays. SMC4 in turn promotes G1/S cell cycle transition, activates TGF-β/SMAD signaling (upregulating p-SMAD2/3, N-cadherin, SNAI1, ZEB1) to enhance metastasis, and facilitates aerobic glycolysis by upregulating LDHA. |
ChIP assay, dual-luciferase reporter, ECAR/OCR metabolic assays, rescue experiments, xenograft and tail-vein metastasis mouse models, cell cycle analysis |
Frontiers in oncology |
Medium |
40933894
|
| 2025 |
SMC4 is identified as a potential substrate of Polo-like kinase 1 (Plk1) in human cells; Plk1 activity is required for chromosome condensation and global chromosomal accessibility during mitosis, and SMC4 is proposed as a downstream effector in this regulatory mechanism. |
5-ethynyl uridine nascent RNA labeling, Plk1 inhibition, ATAC-seq for chromatin accessibility, substrate identification by mass spectrometry |
bioRxivpreprint |
Low |
|
| 2025 |
Solution AFM imaging of yeast condensin in various nucleotide states (AMP-PNP, ATPγS, ADP, no nucleotide) combined with coarse-grained MD simulations of Smc2/Smc4 heterodimer indicates that ATP binding at the head domains induces head engagement coupled to hinge opening, and that the N-terminal region of the Brn1 accessory subunit re-associates with the Smc2 head after ADP release. |
Solution high-speed AFM imaging, coarse-grained molecular dynamics simulation, flexible fitting to AFM images |
bioRxivpreprint |
Medium |
|